Musculoskeletal System - Cartilage Development
|Embryology - 24 Oct 2017 Expand to Translate|
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The musculoskeletal system consists of skeletal muscle, bone, and cartilage and is mainly mesoderm in origin with some neural crest contribution.
The mesoderm forms nearly all the connective tissues of the musculoskeletal system. Each tissue (cartilage, bone, and muscle) goes through many different mechanisms of differentiation. Recent studies show that Sox9 acts as a key regulator of early chondrocyte differentiation.
The intraembryonic mesoderm can be broken into paraxial, intermediate and lateral mesoderm relative to its midline position. During the 3rd week the paraxial mesoderm forms into "balls" of mesoderm paired either side of the neural groove, called somites. Somites appear bilaterally as pairs at the same time and form earliest at the cranial (rostral,brain) end of the neural groove and add sequentially at the caudal end. This addition occurs so regularly that embryos are staged according to the number of somites that are present. Different regions of the somite differentiate into dermomyotome (dermal and muscle component) and sclerotome (forms vertebral column). An example of a specialized musculoskeletal structure can be seen in the development of the limbs.
Skeletal muscle forms by fusion of mononucleated myoblasts to form mutinucleated myotubes. Bone is formed through a lengthy process involving ossification of a cartilage formed from mesenchyme. Two main forms of ossification occur in different bones, intramembranous (eg skull) and endochondrial (eg limb long bones) ossification. Ossification continues postnatally, through puberty until mid 20s. Early ossification occurs at the ends of long bones.
Musculoskeletal and limb abnormalities are one of the largest groups of congenital abnormalities.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Kivanc Gunhan, Serkan Bariskan, Uzdan Uz, Seda Vatansever, Mujde Kivanc 13-93B3 Bioactive Glass: a New Scaffold for Transplantation of Stem Cell-Derived Chondrocytes. J Craniofac Surg: 2017; PubMed 29049142
Gildardo Cortés-Julián, Hussein B Bushra-Nuritu, Renata Buenfil-Fuentes, José A Merino Rajme Modified Ravitch Procedure for Left Poland Syndrome Combined With Pectus Excavatum. Ann. Thorac. Surg.: 2017, 104(4);e337-e339 PubMed 28935331
Beata Żylińska, Ewa Stodolak-Zych, Aleksandra Sobczyńska-Rak, Tomasz Szponder, Piotr Silmanowicz, Mirosław Łańcut, Łukasz Jarosz, Paweł Różański, Izabela Polkowska Osteochondral Repair Using Porous Three-dimensional Nanocomposite Scaffolds in a Rabbit Model. In Vivo: 2017, 31(5);895-903 PubMed 28882956
Wolfgang Härtig, Bianca Mages, Susanne Aleithe, Björn Nitzsche, Stephan Altmann, Henryk Barthel, Martin Krueger, Dominik Michalski Damaged Neocortical Perineuronal Nets Due to Experimental Focal Cerebral Ischemia in Mice, Rats and Sheep. Front Integr Neurosci: 2017, 11;15 PubMed 28860977
Junji Fujikawa, Yuto Takeuchi, Satoshi Kanazawa, Ahmed G Nomir, Akiyoshi Kito, Eman Elkhashab, Amr M Ghaleb, Vincent W Yang, Shigehisa Akiyama, Ichijiro Morisaki, Takashi Yamashiro, Satoshi Wakisaka, Makoto Abe Kruppel-like factor 4 regulates matrix metalloproteinase and aggrecanase gene expression in chondrocytes. Cell Tissue Res.: 2017; PubMed 28856432
- The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 15 the skeletal system
- Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 11 Limb Dev (bone not well covered in this textbook)
- Before we Are Born (5th ed.) Moore and Persaud Chapter 16,17: p379-397, 399-405
- Essentials of Human Embryology Larson Chapter 11 p207-228
- Identify the components of a somite and the adult derivatives of each component.
- Give examples of sites of (a) endochondral and (b) intramembranous ossification and to compare these two processes.
- Identify the general times (a) of formation of primary and (b) of formation of secondary ossification centres, and (c) of fusion of such centres with each other.
- Briefly summarise the development of the limbs.
- Describe the developmental abnormalities responsible for the following malformations: selected growth plate disorders; congenital dislocation of the hip; scoliosis; arthrogryposis; and limb reduction deformities.
Below is a very brief overview using simple figures of 3 aspects of early musculoskeletal development. More detailed overviews are shown on other notes pages Mesoderm and Somite, Vertebral Column, Limb in combination with serial sections and Carnegie images.
|Cells migrate through the primitive streak to form mesodermal layer. Extraembryonic mesoderm lies adjacent to the trilaminar embryo totally enclosing the amnion, yolk sac and forming the connecting stalk.|
|Paraxial mesoderm accumulates under the neural plate with thinner mesoderm laterally. This forms 2 thickened streaks running the length of the embryonic disc along the rostrocaudal axis. In humans, during the 3rd week, this mesoderm begins to segment. The neural plate folds to form a neural groove and folds.|
| Segmentation of the paraxial mesoderm into somites continues caudally at 1 somite/90minutes and a cavity (intraembryonic coelom) forms in the lateral plate mesoderm separating somatic and splanchnic mesoderm.
Note intraembryonic coelomic cavity communicates with extraembryonic coelom through portals (holes) initially on lateral margin of embryonic disc.
|Somites continue to form. The neural groove fuses dorsally to form a tube at the level of the 4th somite and "zips up cranially and caudally and the neural crest migrates into the mesoderm.|
|Mesoderm beside the notochord (axial mesoderm, blue) thickens, forming the paraxial mesoderm as a pair of strips along the rostro-caudal axis.|
|Paraxial mesoderm towards the rostral end, begins to segment forming the first somite. Somites are then sequentially added caudally. The somitocoel, is a cavity forming in early somites, which is lost as the somite matures.|
|Cells in the somite differentiate medially to form the sclerotome (forms vertebral column) and dorsolaterally to form the dermomyotome.|
| The dermomyotome then forms the dermotome (forms dermis) and myotome (forms muscle).
Neural crest cells migrate beside and through somite.
|The myotome differentiates to form 2 components dorsally the epimere and ventrally the hypomere, which in turn form epaxial and hypaxial muscles respectively. The bulk of the trunk and limb muscle coming from the Hypaxial mesoderm. Different structures will be contributed depending upon the somite level.|
- Katsutsugu Umeda, Hirotsugu Oda, Qing Yan, Nadine Matthias, Jiangang Zhao, Brian R Davis, Naoki Nakayama Long-Term Expandable SOX9(+) Chondrogenic Ectomesenchymal Cells from Human Pluripotent Stem Cells. Stem Cell Reports: 2015; PubMed 25818812
- Marcela Buchtova, Veronika Oralova, Anie Aklian, Jan Masek, Iva Vesela, Zhufeng Ouyang, Tereza Obadalova, Zaneta Konecna, Tereza Spoustova, Tereza Pospisilova, Petr Matula, Miroslav Varecha, Lukas Balek, Iva Gudernova, Iva Jelinkova, Ivan Duran, Iveta Cervenkova, Shunichi Murakami, Alois Kozubik, Petr Dvorak, Vitezslav Bryja, Pavel Krejci Fibroblast growth factor and canonical WNT/β-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage. Biochim. Biophys. Acta: 2015; PubMed 25558817
- Toshimi Michigami Current understanding on the molecular basis of chondrogenesis. Clin Pediatr Endocrinol: 2014, 23(1);1-8 PubMed 24532955 | Clin Pediatr Endocrinol.
- Aixin Cheng, Paul G Genever SOX9 determines RUNX2 transactivity by directing intracellular degradation. J. Bone Miner. Res.: 2010, 25(12);2680-9 PubMed 20593410
- Takako Hattori, Catharina Müller, Sonja Gebhard, Eva Bauer, Friederike Pausch, Britta Schlund, Michael R Bösl, Andreas Hess, Cordula Surmann-Schmitt, Helga von der Mark, Benoit de Crombrugghe, Klaus von der Mark SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development: 2010, 137(6);901-11 PubMed 20179096
Masaharu Takigawa CCN2: a master regulator of the genesis of bone and cartilage. J Cell Commun Signal: 2013, 7(3);191-201 PubMed 23794334
| MC3709051 | J Cell Commun Signal. Yasuhiko Kawakami, Joaquín Rodriguez-León, Juan Carlos Izpisúa Belmonte The role of TGFbetas and Sox9 during limb chondrogenesis. Curr. Opin. Cell Biol.: 2006, 18(6);723-9 PubMed 17049221
Mary B Goldring, Kaneyuki Tsuchimochi, Kosei Ijiri The control of chondrogenesis. J. Cell. Biochem.: 2006, 97(1);33-44 PubMed 16215986
Lillian Shum, Glen Nuckolls The life cycle of chondrocytes in the developing skeleton. Arthritis Res.: 2002, 4(2);94-106 PubMed 11879545
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Cite this page: Hill, M.A. 2017 Embryology Musculoskeletal System - Cartilage Development. Retrieved October 24, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Musculoskeletal_System_-_Cartilage_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G